The amount of data related to the biological causes of psychiatric conditions has grown exponentially. Integrating results from all these studies can advance mental health research by increasing statistical power to find biomarkers, reduce false discoveries due to platform-specific technical errors, and increase confidence in findings when multiple lines of evidence point to the same biological factors. Because data integration can involve heterogeneous datasets and biological relations, it also has a considerable potential to improve our understanding of disease mechanisms by elucidating the broader context in which biological factors co-act. This work proposed builds on the long collaboration and complementary expertise of the Van den Oord (VCU) and Sullivan (UNC) labs. The result is a highly coherent, rigorous, and innovative data integration strategy aimed at improving understanding of unique and shared disease mechanisms underlying schizophrenia, bipolar disorder, major depressive disorder, and autism. Specifically: (1) the data sources we will use are deep, comprehensive, and tailored to psychiatry; (2) we developed the MIND package (Mathematically-based Integration of heterogeNeous Data) that is based on a rigorous mathematical framework that allows data integration in a meaningful and statistically optimal fashion. Rather than relying exclusively on simulations, MIND was tested empirically using a large independent replication study showing that it identified biomarkers that would otherwise require far more samples or genetic markers; (3) as we developed methods that can perform independent tests of virtually any kind of biological relationship in all available datasets, diseae mechanisms can be studied in very large samples; and (4) we will make all results and software available via SLEP (Sullivan Lab Evidence Project) for power users and in an user- friendly implementation for end users. Successful completion of the proposed project will (a) allow end users ready access to sophisticated tools for data integration, (b) allow power users to adapt use these resources as they choose, and (c) make an important, high-impact contribution to better understand disease mechanisms underlying psychiatric disorders. PUBLIC HEALTH RELEVANCE: The volume of data related to the biological causes of psychiatric disorders has grown exponentially. Integrating results from all these studies has a considerable potential to improve our understanding of disease mechanisms. This understanding will be critical to improve diagnosis, prevention and treatment.